VDUP1通过在内皮细胞中产生活性氧来增强Ras介导的血管生成。

VDUP1 potentiates Ras-mediated angiogenesis via ROS production in endothelial cells.

作者信息

Piao Z H, Yoon S R, Kim M S, Jeon J H, Lee S H, Kim T D, Lee H G, Bae K H, Min J K, Chung S J, Kim M, Cho Y S, Oh D B, Park S Y, Chung J W, Choi I

机构信息

Korea Research Institute of Bioscience and Biotechnology, Stem Cell Research Center, Daejon, Republic of Korea.

出版信息

Cell Mol Biol (Noisy-le-grand). 2009 Feb 25;55 Suppl:OL1096-103.

PMID:19267992

Abstract

Vitamin D3 up-regulated protein 1 (VDUP1) is a tumor suppressor of which expression is reduced in a variety of cancer cells, and enforced expression inhibits the tumor cell proliferation. It inhibits the activity of thioredoxin, thus contributing cellular ROS generation. Since ROS is a critical factor for angiogenesis, we investigated the role of VDUP1 in angiogenesis and endothelial proliferation. The expression of VDUP1 was upregulated by overexpression of an oncogene, Ras. Enforced expression of VDUP1 increases ROS production and proliferation of Ras-overexpressing endothelial cells. Overexpression of VDUP1 increases the resistance to the anchorage-dependent cell death and tube formation of the Ras-overexpressing endothelial cell. In addition, the removal of ROS by ROS scavenger attenuates the effect of VDUP1 on tube formation. These results suggest that VDUP1 is involved in Ras-mediated angiogenesis via ROS generation in endothelial cells.

摘要

维生素D3上调蛋白1（VDUP1）是一种肿瘤抑制因子，其表达在多种癌细胞中降低，而强制表达则抑制肿瘤细胞增殖。它抑制硫氧还蛋白的活性，从而促进细胞活性氧的产生。由于活性氧是血管生成的关键因素，我们研究了VDUP1在血管生成和内皮细胞增殖中的作用。癌基因Ras的过表达上调了VDUP1的表达。VDUP1的强制表达增加了活性氧的产生以及Ras过表达内皮细胞的增殖。VDUP1的过表达增加了Ras过表达内皮细胞对锚定依赖性细胞死亡的抗性和管形成能力。此外，活性氧清除剂去除活性氧可减弱VDUP1对管形成的影响。这些结果表明，VDUP1通过在内皮细胞中产生活性氧参与Ras介导的血管生成。